Gene delivery using cationic lipids

Polymer. The field of nonviral gene delivery using cationic polymers is at its early stage compared to that of cationic lipid. However, this system is also known to have advantages over lipid-based systems in controlling the size, charge, and other physicochemical properties. Polycation-DNA complexes, also called as polyplexes, are formed by a cooperative... 

Meyer O, et al. Cationic liposomes coated with polyethylene glycol as carriers for oligonucleotides. J Biol Chem 1998 273 15621 Shi G, et al. Efficient intracellular drug and gene delivery using folate receptor-targeted pH-sensitive liposomes composed of cationic/anionic lipid combinations. J Control Release 2002 80 309. 

In this chapter, the synthesis and structure of commonly used cationic lipids for gene delivery and the influence of their physicochemical properties on transfection activity will be described. 

Wang J, Guo X, Xu Y, Barron L, Szoka EC Jr. Synthesis and characterization of long chain alkyl acyl carnitine esters. Potentially biodegradable cationic lipids for use in gene delivery. J Med Chem 1998 41(13) 2207-2215. 

Several major barriers need to be overcome for the development of nonviral gene delivery systems into true therapeutic products for use in humans. These barriers fall into three classes manufacturing, formulation, and stability (extracellular barriers and intracellular barriers) (85). Cationic lipids and cationic polymers self-assemble with DNA to form small particles that are suitable for cellular uptake. At the therapeutic doses positively charged particles readily aggregate as their concentration increases, and are quickly precipitated above their critical flocculation concentration. 

Successful gene delivery by use of cationic liposomes requires the following conditions (134) (1) condensation of DNA into the complex and its protection from degradation by intracellular nucleases (2) adhesion of DNA-lipid complex onto the cellular surface (3) complex internalization (4) fusion of an internalized DNA-cationic liposome complex with the endosome membrane (5) escape of DNA from the endosome (6) entry of DNA into the nucleus followed by gene expression. 

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